Ion analysis system and method with multiple ionization sources and analyzers

ABSTRACT

An ion analysis system includes one or more ionization sources that produce ions, one or more analyzers that analyze the ions based on ion mobility or mass to charge ratio of the ions, and one or more ion transfer devices connected between the one or more ionization sources and the one or more analyzers, the one or more ion transfer devices include a plurality of electrodes that are configured to be flexible or flexibly connected to each other, and the one or more ion transfer devices are configured to be flexible or re-configurable while transferring the ions.

RELATED APPLICATIONS

The present application is a continuation and claims the prioritybenefit of U.S. patent application Ser. No. 16/350,396 (now U.S. Pat.No. 10,720,315), which claims priority to Provisional Application No.62/680,592 entitled: “Flexible Ion Guide,” filed on Jun. 5, 2018; thecontents and disclosures of which are hereby incorporated by referencein their entireties herein and below.

TECHNICAL FIELD

The present disclosure relates to an ion transfer device. In particular,the present disclosure is related to an ion transfer device that isflexible or re-configurable and may be bent or re-configured from oneshape to another shape while transferring ions produced from a sample ina first location using an ion source (such as an ionization probe) to anion analyzer (such as a mass spectrometer or an ion mobility analyzer)in the second location. The ions may be transferred inside the iontransfer device in sequentially-packed ion packets.

BACKGROUND

Mass spectrometry and ion mobility spectrometry are analyticaltechniques for chemical analysis to detect and identify analytes ofinterest in various applications. With the increased use of theseinstruments, their applications and the variety of applications haveincreased. However, their size still remains large, hindering theirapplications in point of care/action/need applications, where size andportability is limiting.

A mass spectrometer is a complex system composed of various components,as shown in FIG. 1A. The critical components of a typical massspectrometer consist of sample introduction and ionization 1, samplinginlet 2, ion optics and mass analyzer 4, detector 5, vacuum chamber orhousing 3, vacuum system 9 including vacuum pumps and gauges, voltagesupply systems 6, control systems 7, and data acquisition systems 8. Ina typical mass spectrometer, first, the ionization source 1 ionizes asample to generate positive and negative ions. The generated ions travelthrough the sampling inlet 2 and are guided, for example by ion guides,such as an ion funnel and/or multipole ion guides, to enter the massanalyzer 4. All of these components are closely connected to each other.The mass analyzer 4, which is derived by voltage supply systems 6,separates ions based on their m/z. The detector 5 produces an electricalsignal when the ions hit the detector 5. The data acquisition systems 8receive the electrical signal from the detector 5, typically in the formof electrical current or voltage, and produce and record spectra. Thespectra provide fingerprints for chemical identification of the sample.Control systems 7 control various components. All components related tothe mass analysis and ion detection are placed inside a vacuum chamber3, maintained at high vacuum. Although FIG. 1A shows sampleintroduction/ionization block 1 outside the vacuum region, ionization ofsamples may occur in a wide range of pressures, from atmosphericpressure to high vacuum. In a conventional mass spectrometer, the sampleintroduction/ionization 1 is attached to the sampling inlet 2.

Mass spectrometers require high vacuum for proper operation because,ideally, ions must travel inside a mass spectrometer without collidingwith background gas molecules. Therefore, the vacuum in the massanalyzer 4 of a mass spectrometer must be maintained at a pressure thatcorrelates with ion mean free path length longer (ideally several folds)than the length of the mass analyzer. According to the kinetic theory ofgases, the mean free path L (in m) is given by: L=kT/√2 pσ, where k isthe Boltzmann constant, T is the temperature (in K), p is the pressure(in Pa), and σ is the collision cross-section (in m²). In a typical massspectrometer with k=1.38×10⁻²¹ JK⁻¹, T=300 K, and σ=45×10⁻²⁰ m², themean free path equation simplifies to L=4.95/p, where L is incentimeters and p is in milli-Torn In laboratory-scale massspectrometers, ion filtering and detection usually occur in high vacuum,i.e. <10⁻⁵ Torr, corresponding to a mean free path of >4.95 meters. Thisis necessary to achieve high resolution separation of ions. To achieve apressure of <10⁻⁵ Torr with available vacuum technologies, a two-stagevacuum generation process is utilized. First, the pressure is reduced to˜10⁻² Torr using mechanical or roughing pumps, and then one or moreturbo-molecular pumps, ion pumps, or cryogenic pumps further reduce thepressure to <10⁻⁵ Torr. Turbo-molecular pumps provide relatively higherpumping capacities compared to ion pumps and are more appropriate foratmospheric pressure sampling and ionization. Ion pumps have advantageswhen vibration-free operation and ultra-high vacuum is required (vacuumlevels of <10⁻¹⁰ Torr).

Prior to the introduction of soft ionization and ambient ionizationtechniques, mass spectrometry was generally limited to the analysis ofvolatile, relatively low-molecular-mass samples, and mass spectrometricanalysis of biomolecules was difficult if not impossible. Also,conventional ionization sources, such as electron impact ionization,caused excessive fragmentation when applied to biomolecules. The adventof soft ionization techniques, which produce mass spectra with little orno fragmentation in ambient or near-ambient environment, made itpossible to analyze large organic molecules and biomolecules with massspectrometers. In particular, the development of electrospray ionization(ESI) and matrix-assisted laser desorption/ionization (MALDI) hasextended the application of mass spectrometry to biomolecules. Thesetechniques have demonstrated unparalleled advantages, for example inanalyzing peptides and proteins, because of the speed of experiments,the amount of information generated, and the outstanding resolution andsensitivities offered.

Among various soft ionization techniques, ESI sources are best suitedfor direct biomolecules. ESI may function as a liquid sampleintroduction system and an ionization source at the same time. In ESI,the sample in a solution (typically a 50/50 mixture of water/methanolwith 0.1-1% acetic or formic acid) enters a narrow capillary and leavesthe capillary as a liquid spray. The voltage at the end of the capillaryis significantly higher (3 to 5 kV) than that of the mass analyzer, sothe sample is sprayed or dispersed into an aerosol of highly chargeddroplets. Evaporation of solvent decreases the size of the droplets.Because the electrically charged droplets retain their charge but getsmaller, their electric field increases. At some point, mutual repulsionbetween like charges causes ions to leave the surface of the droplet. Asa result, multiply charged ions from individual biomolecules, free fromsolvent, are released and enter the sampling inlet for analysis by themass spectrometer.

Except for MALDI and similar ionization methods that ionize samples inthe high-vacuum region, most mass spectrometry techniques for analyzingbio-molecules rely on interfaces or sampling inlets that delivergas-phase molecular ions from atmospheric pressure or near atmosphericpressure to high vacuum through orifices or capillaries. Achieving highion transfer efficiencies for mass spectrometers is crucial andchallenging. Conductance limiting orifice plates enable differentialpumping of various stages of a mass spectrometer. Smaller orificesenable operation with lower pumping capacities but result in lower iontransfer efficiencies. Larger-diameter orifices may improve theefficiency of ion transfer but allow more neutrals to enter the vacuumregion, thus requiring larger, higher-speed pumps to maintain thedesired vacuum. Therefore, the pumping capacity of the vacuum systemindirectly determines the ion transfer efficiency, because the size anddimensions of the sampling inlet must be designed according to thepumping capacity of the vacuum system. Finding the right balance betweenthe pumping capacity and the ion transfer efficiency is a challengingdesign consideration for mass spectrometers if a limited pumpingcapacity is available.

Various sampling mechanisms are developed to address the above-notedchallenges, such as the discontinuous atmospheric pressure interface(DAPI) and the pulsed pinhole atmospheric pressure interface (PP-API).The continuous atmospheric pressure interface enabled by differentialpumping is another sampling mechanism that uses multi-stage vacuum pumpsfor differential pumping, to provide gradual pressure reduction totransport ions from atmospheric pressure to high vacuum. The extent towhich the motion of ions may be controlled in different vacuum stagesdetermines the overall ion transmission efficiency of the massspectrometer. Recently, ion funnels have attracted significant interestin atmospheric pressure sampling in addition to the conventionalmultipole ion guides. Ion funnels enable the manipulation and focusingof ions in a pressure regime (0.01 to 30 Torr), providing much greaterion transmission efficiencies. Usually, ion funnels are located rightafter heated capillary inlets in a mass spectrometer. Ion funnels arerigid structures that guides ions in mid-vacuum level of 0.01 to 30Torr. In ion funnels, the spacing between ring electrodes are constant.

Mass analyzers are the core components of mass spectrometers and aretypically characterized by their mass range and resolution. Mass rangeis the maximum mass resolvable mass by the analyzer. Resolution is anindicator of how selective a mass filter is in distinguishing ions withm/z that are close in value. Thus far, various mass analyzers withdifferent mechanisms have been developed. General mass spectrometryhandbooks provide detailed descriptions of various mass analyzers. Massanalyzers may be categorized into beam analyzers, such as quadrupole andTOF analyzers, and trapping analyzers, such as ion traps.

Faraday cups and micro channel plate (MCP) detectors are the two mostwidely used ion detectors in mass spectrometry. Faraday cups may operateat high pressures (up to atmospheric pressure), but are less sensitive,and are not compatible with high-resolution mass spectrometry due toslow response times. MCPs support high mass resolution, dynamic range,and detection sensitivity. Most modern MCP detectors consist of twoMCPs, with angled channels rotated 180° from each other, producing achevron (v-like) shape. The angle between the channels reduces ionfeedback. In a chevron MCP, the electrons that exit the first plateinitiate the cascade in the next plate. The advantage of the chevron MCPover the straight channel MCP is significantly more gain at a givenvoltage. The two MCPs may either be pressed together or have a small gapbetween them to spread the charge across multiple channels.

With the advent of ambient desorption ionization sources, which desorband ionize molecules in their native state, the applications of massspectrometers have been extended significantly. For example, ambientdesorption ionization techniques may be used to analyze human tissuesduring a surgery to differentiate cancer cells. As another example,ambient ionization desorption techniques may be used in homelandsecurity to monitor cargo and passengers at security check points forexplosives. Three different scenarios have been used thus far for suchapplications. In the conventional method shown in FIG. 1B, the samplesare brought close to a mass spectrometer for ionization and analyses. Inthis approach, samples are directly place in front of a massspectrometer. In a second approach shown in FIG. 1C, samples or samplemolecules are transferred through a bare tube 19, which may be plasticor metal, into the ion source 11 of the mass spectrometer. A samplingmedium, such as water, may be used to mix sample with sampling medium tobe transferred through the bare tube to a mass spectrometer. In thethird approach shown in FIG. 1D, samples are ionized using an ion sourcethat is detached from a mass spectrometer and the produced ions aretransferred via the bare tube 19 to a mass spectrometer for analysis.All of these approaches have disadvantages. For example, placing asample directly in front of a mass spectrometer (FIG. 1B) may not bepractical in many applications, particularly when the sample is bulky orimmobile. Second transferring sample molecules via the bare tube 19 to amass spectrometer (FIG. 2B) may result in memory effects from sampleresidue/molecules sticking to the inner surface of the bare tube 19.These residues may contaminate the inner side of the bare tube 19 andmay adversely affect the analytical results. Transferring ions throughbare tube 19, as shown in FIG. 1D, may result in decreased ion transferefficiency as a majority of ions are lost to the inner walls of the baretube 19 and deteriorate ion transfer efficiency. In other words, the iontransfer efficiency of this method may not be sufficient, and a majorityof ions may be lost in the ion transfer process, thus negativelyaffecting analytical performance.

SUMMARY

One or more embodiments of the present disclosure relates to a flexibleion transfer device that may transfer ions from a first location to asecond location, such that the first location may be in a proximity ofwhere samples to be analyzed are located and the second location iswhere a mass spectrometer is located. Mass spectrometers are still bulkybut the growing demand of mass spectrometers in point ofneed/care/action, such as medical and security applications requirehaving mass spectrometers more accessible. With the conventional massspectrometers, that is not possible because mass spectrometers are bulkyand large. Further, ambient ionization techniques produce ions fromsamples in their native environment (such as human tissues duringsurgery to detect cancer cells). Therefore, the present disclosure aimsto provide an improvement over the state-of-the-art by providing aflexible ion transfer device that may be connected between an ambiention source (which may be constructed as an application-specific orgeneral-purpose ionization probe) in first location and a massspectrometer in a second location such that the ions produced by the ionsource may be efficiently transferred to a mass spectrometer via theflexible ion transfer device. The flexible ion transfer device providesan advantage that an operator/user may easily move the ion sourceto/around the sample and may produce ions for mass spectrometry analysiswithout having to bring a mass spectrometer closer to a sample undertest. Further, various ion sources or ion source probes may be attachedto a single mass spectrometer, which results in more efficient use of amass spectrometer. It is noted that the sample analysis in a massspectrometer from the moment ions are produced to the moment the ionsare detected by the detector takes milli-seconds to a few seconds.Therefore, mass spectrometers are ideally able to provide continuousanalysis every few seconds at most. However, the sample introductiontechniques are currently a limiting factor of the process. The time inbetween two mass spectrometric analyses currently lag behind a massspectrometers ideal throughput because of the slow sample introduction.Therefore, producing a sequence of ions packets to be analyzed by a massspectrometer will significantly improve throughput of mass spectrometryanalysis. For example, sequentially packed ions may be produced fromvarious ionization sources and may be queued and transferred to a massspectrometer for analysis, thus increasing throughput of analyses. Thepresent disclosure provides an ion transfer device and an ion transfermethod for producing ions in a remote location and for transferring theproduced ions sequentially to a mass spectrometer for analysis.

In one or more embodiments, an ion transfer device transfers ions fromat least one ion inlet to at least one ion outlet of the ion transferdevice, and the ion transfer device includes an enclosure configured tomaintain reduced pressure; and a plurality of electrodes disposed atleast in part inside the enclosure such that the ion transfer device isconfigured to be flexible or re-configurable.

In one or more embodiments, the ion transfer device is configured to bebent from two or more bend positions to form a plurality of curvatureswhile actively and efficiently transferring the ions.

In one or more embodiments, the plurality of electrodes are flexiblyconnected to each other to make the ion transfer device re-configurablewhile actively transferring the ions from a first location to a secondlocation.

In one or more embodiments, the one or more ion transfer enclosures andone or more electrodes are flexibly attached to each other to allow theion transfer device to transfer the ions in two or more differentshapes.

In one or more embodiments, the ion transfer device is configured to betransformable between two or more different physical shapes, and the iontransfer device is configured to transfer the ions in the two or moredifferent physical shapes from the at least one ion inlet to the atleast one ion outlet.

In one or more embodiments, the reduced pressure in which an iontransfer device is maintained at is between 0.001 to 100 Torr.

In one or more embodiments, the ion transfer device is re-configurableand transformable between at least a first configuration and a secondconfiguration such that the ion transfer device, in the firstconfiguration, transfers ions from a first location to a secondlocation, and the ion transfer device, in the second configuration,transfers the ions from the first location to a third location, thethird location being different from the second location.

In one or more embodiments, at least two of the plurality of electrodesare configured to be flexibly attached to each other using electricallyinsulating material.

In one or more embodiments, a first group of electrodes include a firstnumber of the plurality of electrodes are attached to each other in anon-flexible manner, a second group of electrodes including a secondnumber of the plurality of electrodes are attached to each other in anon-flexible manner, and the first group of electrodes and the secondgroup of electrodes are attached to each other in a flexible manner toallow bending of the first group of electrodes or the second group ofelectrodes around one or more axes with respect to each other.

In one or more embodiments, the plurality of electrodes are ring-shapedelectrodes that form an elongated ion funnel structure.

In one or more embodiments, the plurality of electrodes are wires inhelical form.

In one or more embodiments, the plurality of electrodes are disposedparallel to each other and are elongated along an axis of the iontransfer device.

In one or more embodiments, the plurality of electrodes are attached toan inner surface of the enclosure.

In one or more embodiments, RF voltage and DC voltage are applied toeach of the plurality of electrodes, and the RF voltage and DC voltageare applied to each of the plurality of electrodes respectively via acapacitor and a resistor.

In one or more embodiments, the DC voltage is traveling DC voltagepulse.

In one or more embodiments, RF voltage applied to each of the pluralityof electrodes is out of phase with the RF voltage applied to adjacentelectrodes.

In one or more embodiments, the DC voltage causes the ions to moveaxially parallel to an axis of the ion transfer device, and the RFvoltage causes the ions to move radially around the axis of the iontransfer device.

In one or more embodiments, the ion transfer device is connected to anion source that is configured to be freely movable in 3-dimensionalspace to bring it in close to a sample under test to produce the ionsfrom the sample under test.

In one or more embodiments, an ion analysis system includes at least oneion source configured to produce ions from a sample; at least one iontransfer device having an enclosure, and a plurality of electrodesdisposed at least in part inside the enclosure such that the iontransfer device is configured to be flexible or re-configurable; and amain body having at least one analyzer configured to separate the ionsbased on mobility or mass to charge ratio; and at least one detectorconfigured to detect the separated ions.

In one or more embodiments, a method includes producing ions from asample; transferring the ions with at least one ion transfer device thatis configured to be flexible or re-configurable, the ion transfer devicehaving an enclosure, and a plurality of electrodes disposed at least inpart inside the enclosure; separating the ions with at least oneanalyzer configured to separate the ions based on mobility or mass tocharge ratio; and detecting the separated ions with at least onedetector.

BRIEF DESCRIPTION OF DRAWINGS

Certain embodiments of the present disclosure are described withreference to the accompanying drawings. However, the accompanyingdrawings illustrate only certain aspects or implementations of thepresent disclosure by way of example and are not meant to limit thescope of the claims.

FIG. 1A shows a block diagram of a conventional mass spectrometer.

FIG. 1B shows a block diagram of a conventional mass spectrometer.

FIG. 1C shows a block diagram of a conventional mass spectrometer suchthat the ion source is detached from the ion guide and the ions aretransferred to ion guide of a mass spectrometer via a bare tube.

FIG. 1D shows a block diagram of a conventional mass spectrometer suchthat the sample is located at a distance from the ion source and theions are transferred to ion source of a mass spectrometer via a baretube.

FIG. 2A shows a block diagram of a mass spectrometry system such thatthe ion source is detached from the ion guide and the ions areefficiently transferred to ion guide via a flexible or re-configurableion transfer device in accordance with one or more embodiments of thepresent disclosure.

FIG. 2B shows a block diagram of a mass spectrometry system such thatthe ion source in form of an ion source probe is detached from the ionguide and the ions are efficiently transferred to the ion guide via aflexible or re-configurable ion transfer device in accordance with oneor more embodiments of the present disclosure.

FIG. 2C shows a block diagram of a mass spectrometry system such thatthe ion source is detached from the mass spectrometer and the ionsproduced in an ionization probe are efficiently transferred to the massspectrometer via a flexible or re-configurable ion transfer device inaccordance with one or more embodiments of the present disclosure.

FIG. 2D shows a block diagram of a mass spectrometer such that the ionsource is detached from the mass spectrometer and the ions produced inan ionization probe are efficiently transferred to the mass spectrometervia a flexible or re-configurable ion transfer device in accordance withone or more embodiments of the present disclosure.

FIG. 2E shows a block diagram of a mass spectrometry system such thatthe ion source is detached from the ion guide and the ions areefficiently transferred to ion guide via a flexible or re-configurableion transfer device in accordance with one or more embodiments of thepresent disclosure.

FIG. 2F shows a block diagram of a mass spectrometry system such thatthe ion source is detached from the ion guide and the ions areefficiently transferred to ion guide via a flexible or re-configurableion transfer device in accordance with one or more embodiments of thepresent disclosure.

FIG. 3A shows a block diagram of a mass spectrometry system such thatthree different ion sources are attached to mass spectrometry system viaflexible or re-configurable ion transfer devices in accordance with oneor more embodiments of the present disclosure.

FIG. 3B shows a block diagram of a mass spectrometry system such thatthree different ion sources are efficiently transfer ions to twodifferent mass spectrometry systems via flexible or re-configurable iontransfer devices in accordance with one or more embodiments of thepresent disclosure.

FIG. 4A, FIG. 4B, FIG. 4C, and FIG. 4D show block diagrams of differentconfigurations for ion transfer devices in accordance with one or moreembodiments of the present disclosure.

FIG. 5A, FIG. 5B, and FIG. 5C show block diagrams of differentconfigurations of ion transfer device in accordance with one or moreembodiments of the present disclosure.

FIG. 6A, FIG. 6B, FIG. 6C, and FIG. 6D show perspective views offlexible or re-configurable ion transfer device in accordance with oneor more embodiments of the present disclosure.

FIG. 7A and FIG. 7B show perspective views of flexible orre-configurable ion transfer device in accordance with one or moreembodiments of the present disclosure.

FIG. 8A, FIG. 8B, and FIG. 8C show front views of electrodes of flexibleor re-configurable ion transfer device in accordance with one or moreembodiments of the present disclosure.

FIG. 9A, FIG. 9B, FIG. 9C, FIG. 9D, and FIG. 9E show cross-section viewsof electrodes of flexible or re-configurable ion transfer deviceconnected to each other in accordance with one or more embodiments ofthe present disclosure.

FIG. 10A and FIG. 10B show perspective views of electrode structure offlexible or re-configurable ion transfer device in accordance with oneor more embodiments of the present disclosure.

FIG. 11A, FIG. 11B, and FIG. 11C show perspective views of flexible orre-configurable ion transfer device including three electrode structuresconnected to each other in accordance with one or more embodiments ofthe present disclosure.

FIG. 12A and FIG. 12B show perspective views of flexible orre-configurable ion transfer device including seven electrode structuresconnected to each other in accordance with one or more embodiments ofthe present disclosure.

FIG. 13 shows a perspective view of flexible or re-configurable iontransfer device including two electrode structures connected to eachother accordance with one or more embodiments of the present disclosure.

FIG. 14A, FIG. 14B, and FIG. 14C show perspective views of enclosure andelectrode geometries of flexible or re-configurable ion transfer devicein accordance with one or more embodiments of the present disclosure.

FIG. 15A, FIG. 15B, and FIG. 15C show perspective views of flexible orre-configurable ion transfer devices in accordance with one or moreembodiments of the present disclosure.

FIG. 16 shows a perspective view of electrode geometry of flexible orre-configurable ion transfer device in accordance with one or moreembodiments of the present disclosure.

FIG. 17A and FIG. 17B show two side views of ion trajectory simulationin flexible or re-configurable ion transfer device in accordance withone or more embodiments of the present disclosure.

FIG. 18 shows RF and DC voltage waveforms for flexible orre-configurable ion transfer device in accordance with one or moreembodiments of the present disclosure.

FIG. 19 shows RF and DC voltage waveforms for flexible orre-configurable ion transfer device in accordance with one or moreembodiments of the present disclosure.

FIG. 20 shows a flow chart of a method for transferring ions withflexible or re-configurable ion transfer device in accordance with oneor more embodiments of the present disclosure.

FIG. 21 shows a block diagram of control unit for ion transfer deviceupon which one or more embodiments of the present disclosure may beimplemented.

DETAILED DESCRIPTION

In general, embodiments of the present disclosure related to a flexibleor re-configurable ion transfer device and methods for transferring ionswith a flexible or re-configurable ion transfer device.

Specific embodiments are disclosed with reference to the accompanyingdrawings. In the following description, numerous details are set forthas examples of the present disclosure. It will be understood by thoseskilled in the art that one or more embodiments of the presentdisclosure may be practiced without these specific details and thatnumerous variations or modifications may be possible without departingfrom the scope of the invention. Certain details known to those ofordinary skill in the art are omitted to avoid obscuring thedescription.

FIG. 2A shows a block diagram of a mass spectrometry system such thatthe ion source 21 is detached from the ion guide 13 and the ions areefficiently transferred to ion guide via a flexible or re-configurableion transfer device 20 in accordance with one or more embodiments of thepresent disclosure. The mass spectrometry system, as disclosed herein,may include the ion source 21, the ion transfer device 20, the ion guide13, the mass analyzer 15, the detector 17, and the corresponding vacuumsystems and electronics (additional sub-systems) for proper operationand full functionality. Additional sub-systems for a mass spectrometerare shown in FIG. 1A and omitted in this and other figures of thepresent application to avoid obscuring the description and drawings andfor maintaining simplicity of illustration. One of ordinary skill in theart, in view of the present disclosure, will understand that the massspectrometry system includes additional sub-systems such as those shownin FIG. 1A for full functionality and operation.

In FIG. 2A, the mass spectrometry system includes an ion source 21 thatis detached from an ion guide 13 of the mass spectrometry system and theions are efficiently transferred from the ion source 21 to the ion guide13 of the mass spectrometry system through the ion transfer device 20,which is flexible or re-configurable. The ion guide 13 may be one ormore ion funnels, or one or more multipole ion guides having a pluralityof even number of poles used in conventional mass spectrometers. The ionsource 21 may be electrospray, plasma, glow discharge, laser,photo-ionization, or a combination of them used in ambient ionizationtechniques. In one or more embodiments, the ion source 21 may use anyambient ionization techniques under categories “extraction” (a solid orliquid extraction processes dynamically followed by spray or chemicalionization), “plasma” (thermal or chemical desorption with chemicalionization), “two-step” (desorption or ablation followed by ionization),“laser” (laser desorption or ablation followed by ionization),“acoustic” (acoustic desorption followed by ionization), or multimode(involving two of the above modes).

In one or more embodiments, the ion source 21 may be any of Airflow-assisted ionization, Air flow-assisted desorption electrosprayionization, Atmospheric pressure glow discharge desorption ionization,Ambient pressure pyroelectric ion source, Atmospheric pressure thermaldesorption chemical ionization, Atmospheric pressure thermaldesorption/ionization, Atmospheric pressure solids analysis probe, Betaelectron-assisted direct chemical ionization, Charge assisted laserdesorption/ionization, Desorption atmospheric pressure chemicalionization, Desorption atmospheric pressure photoionization, Directanalysis in real time, Dielectric barrier discharge ionization,Desorption corona beam ionization, Desorption chemical ionization,Desorption electro-flow focusing ionization, Desorptionelectrospray/metastable-induced ionization, Desorption electrosprayionization, Desorption sonic spray ionization, Desorption ionization bycharge exchange, Direct inlet probe-atmospheric-pressure chemicalionization, Direct probe electrospray ionization, Electrode-assisteddesorption electrospray ionization, Easy ambient sonic-spray ionization,Extractive electrospray ionization, Electrospray laser desorptionionization, Electrospray-assisted pyrolysis ionization, Electrostaticspray ionization, Flowing atmospheric pressure afterglow, Field-induceddroplet ionization, High-voltage-assisted laser desorption ionization,Helium atmospheric pressure glow discharge ionization, Infrared laserablation metastable-induced chemical ionization, Jet desorptionelectrospray ionization, Laser assisted desorption electrosprayionization, Laser ablation electrospray ionization, Laser ablationflowing atmospheric pressure afterglow, Laser ablation inductivelycoupled plasma, Laser desorption atmospheric pressure chemicalionization, Laser diode thermal desorption, Laser desorptionelectrospray ionization, Laser desorption spray post-ionization, Laserelectrospray mass spectrometry, Liquid extraction surface analysis,Laser-induced acoustic desorption-electrospray ionization, Liquidmicro-junction-surface sampling probe, Leidenfrost phenomenon-assistedthermal desorption, Liquid sampling-atmospheric pressure glow discharge,Laser spray ionization, Low temperature plasma, Matrix-assisted inletionization, Matrix-assisted laser desorption electrospray ionization,Microfabricated glow discharge plasma, microwave induced plasmadesorption ionization, Nano-spray desorption electrospray ionization,Neutral desorption extractive electrospray ionization, Plasma-assisteddesorption ionization, Paint spray, Plasma-assisted laser desorptionionization, Plasma-assisted multiwavelength laser desorption ionization,Plasma-based ambient sampling/ionization/transmission, Paper assistedultrasonic spray ionization, Probe electrospray ionization, Paper spray,Pipette tip column electrospray ionization, Radiofrequency acousticdesorption and ionization, Remote analyte sampling transport andionization relay, Rapid evaporative ionization mass spectrometry,Robotic plasma probe ionization, Surface activated chemical ionization,Solvent-assisted inlet ionization, Surface acoustic wave nebulization,Secondary electrospray ionization, Solid probe assistedNano-electrospray ionization, Single-particle aerosol mass spectrometry,Sponge-Spray Ionization, Surface sampling probe, Switched ferroelectricplasma ionizer, Thermal desorption-based ambient mass spectrometry,Transmission mode desorption electrospray ionization, Touch spray,Ultrasonication-assisted spray ionization, Venturi easy ambientsonic-spray ionization, Brush-Spray Ionization, or Fiber-SprayIonization.

In one or more embodiments, re-configurable or flexible in the presentdisclosure is defined as the capability of being transformed between atleast two different shapes or forms, or being transformed from oneconfiguration to another configuration. In one or more embodiments, thistransformation occurs and a shape or a form of the ion transfer device20 is changed when ions are being actively transferred by the iontransfer device 20. The ion transfer device 20 may have a plurality ofbend positions 12 a and 12 b, and the ion transfer device may form oneor more curvatures around the bend positions. In one or moreembodiments, the flexible or re-configurable ion transfer device 20 mayhold or retain a new shape or form after changing the shape or form froman old shape to a new shape, for example, by a force applied by hands ofa user or an operator. In one or more embodiments, the flexible orre-configurable ion transfer device 20 may be soft and may not retain orhold a new shape or form after changing the shape or form from an oldshape to the new shape. In one or more embodiments, flexible orre-configurable in the present disclosure is defined as the capabilityof being bent and being able to change from an old form or shape to anew form or shape when the ion transfer device 20 is activelytransferring the ions. In one or more embodiments, flexible orre-configurable may be defined as the ion transfer device 20 having aplurality of bend positions such that the ion transfer device 20 mayform curvatures. In one or more embodiments, flexibility is defined asthe achievable range of motion or being at a bend position or aplurality of bend positions without affecting ion transfer efficiency ofthe ion transfer device 20, without losing the functionality of the iontransfer device 20, or without shorting electrical connections of theion transfer device 20. In one embodiment, flexible is defined as beingcapable of having a plurality of curvatures around an axis of the iontransfer device 20. In one embodiment, flexibility of the ion transferdevice 20 may or may not retain a form or a shape while being flexibleor re-configurable. In one or more embodiments, flexibility may bedefined as spacing between electrodes of the ion transfer device 20being increased or decreased. In one or more embodiments, being flexibleand being re-configurable may be used in an interchangeable manner.

The ion transfer device 20 has a diameter and a length. The diameter maybe the same or different along the ion transfer device 20. In one ormore embodiments, the diameter of the ion transfer device 20 may be anyvalue between 0.2 to 2 inches or even up to 5 inches, the length of theion transfer device 20 may be any value between 0.5 to 1000 inches, or 1to 500 feet. In one or more embodiments, the length may be 2, 5, 10, 100or even 1000 times of the diameter (or the largest or the smallestdiameter if the diameter varies along the length). The length is as thedistance between defined the point the ion transfer device 20 isconnected to the ion source 21, (or for example the ion inlet of the iontransfer device 20) and the point the ion transfer device 20 isconnected to the ion guide 13 (or for example the ion outlet of the iontransfer device 20) when the ion transfer device 20 is in the form of astraight-line between these two points. The ion inlet (illustrated indrawings as “ions in”) and the ion outlet (illustrated in drawings as“ions out”) in the present disclosure are defined as sides of iontransfer device from which ions respectively enter and exit the iontransfer device 20.

FIG. 2B shows a block diagram of a mass spectrometry system such thatthe ion source probe 22 is detached from the ion guide 13 and ions areefficiently transferred to ion guide 13 via a flexible orre-configurable ion transfer device 20 in accordance with one aspect ofthe present disclosure. The mass spectrometry system shown in FIG. 2Bincludes a flexible ion transfer device 20, which may efficientlytransfer ions from a hand-held or portable ionization probe 22 to an ionguide 13 of a conventional mass spectrometer that also includes a massanalyzer 15 and a detector 17.

The terms “Efficient” or “efficient transfer” of ions or “efficient iontransfer,” or “efficiently transferring ions” are defined in the presentdisclosure as the transfer of ions with no ion loss or with minimalloss. The ion loss may be caused by collisions of ions with the innerwalls of the ion transfer device 20 or by colliding with structuresdisposed inside the ion transfer tube 20. In some embodiments, efficiention transfer may be ion transfer with the ratio of ion exiting the ionoutlet of the ion transfer device 20 to the ions entering the ion inletof the ion transfer device 20 being greater than 0.99, 0.95, 0.90, 0.85,0.80, 0.5, 0.2 or 0.1. In one or more embodiments, ion transferefficiency is defined as the ratio of “the ion exiting the outlet of theion transfer device when all required voltages for the ion transferdevice operation is applied” to “the ions exiting the outlet of the iontransfer device 20 when no voltage is applied to the ion transfer device20” being greater than, for example, 1.5, 2, 3, 10, 50, 500, 1000, orbeing greater than 1000 or more. In one or more embodiments, efficientmay be defined as the percentage of ions exiting the outlet of the iontransfer device 20. The efficiency may be greater than 90%, 50%, or 10%.The number of ions entering the ion inlet or exiting the ion outlet ofthe ion transfer device 20 may be measured or quantified, for example,by monitoring ion current at the ion inlet or ion outlet of the iontransfer device 20 with ion current detector such as an ammeter, anelectrometer, or an electron multiplier. In one or more embodiments,Active ion transfer or actively transferring ions in the presentdisclosure is defined as transfer of ions with aid of electric fields orpotentials created by application of voltages to electrodes of the iontransfer device 20 or when various voltages (such as DC or RF or acombination of both) are applied to electrodes of the ion transferdevice 20. Transfer or movement of ions inside the ion transfer device20 may be under an effect of electric field, or gas flow, or acombination of both. Further, ion-ion repulsion may move ions inside theion transfer device 20.

The pressure inside the ion transfer device may be in the range of 0.001to 760 Torr. In this pressure regime, the ions have a relatively smallmean free path, (in the order of a few nanometers to severalmicrometers), and therefore, collision of ions with background gasexists inside the ion transfer device 20 and when ions are beingtransferred or guided inside the ion transfer device 20. The collisionof ions with the background gas (for example air molecules) in thesepressure regimes results in ions not travelling in straight lines andfrequently colliding with background gas molecules and changing path asa result of these collisions. Out of phase RF voltages (or alternatingcurrent (AC) voltages) are used in conjunction with DC voltages toefficiently guide and transfer the ions inside ion transfer device 20.RF voltages radially push ions towards a central axis of the iontransfer device 20 and maintain ions in a central portion of the iontransfer device 20, thus preventing ions from colliding with inner wallsand being lost. While RF voltages and the resulting electric field fromRF voltages retain ions in a central portion of the ion transfer device20 (for example along a longitudinal axis of the ion transfer device20), the DC voltage may provide a gradient to transfer and guide theions in a direction towards ion outlet of the ion transfer device 20.

The ion transfer device 20 may be in a shape of a flexible tube or aflexible bellow with a plurality of electrodes disposed inside theflexible tube or bellow to receive the ions from an ion inlet of the iontransfer tube 20 from an ionization source, such as the hand-heldionization probe 22, and then actively transfer the ions to an ionoutlet of the ion transfer device 20, where ions then enter the ionguide 13 of the mass spectrometer.

It is noted that although the present disclosure mainly describes use ofa mass spectrometer to describe operation of the ion transfer device 20,however, one of ordinary skill in the art will recognize and understandthat the present disclosure may also relate to an ion mobilityspectrometer or any other apparatus that transfers gas phase ions. Ionsin the present disclosure are defined as charged particles, havingpositive or negative charges. Therefore, all the examples in which amass spectrometer is described may be similarly applied to an ionmobility spectrometer, or any other apparatus using an ions orelectrons, or any charged particles. In one or more embodiments, ionsare atoms or molecules with a net electric charge due to the loss orgain of one or more electrons, and the atoms or molecules may be thesame or different.

The ion transfer device 20 may include a tube made from a single partsuch as a plastic or metal tube or made from multiple tubes that areconnected to each other. One or more layers of tubes may be used toprovide vacuum-tightness and also for housing wires, capacitors,resistors and electrodes in between different layers of tubing. Theplastic tube may be a heat-shrink tube. Heat-shrink tube may be made ofany one of thermoplastics, including polyolefin, polyvinyl chloride(PVC), Viton® (for high-temp and corrosive environments), Neoprene®,polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP) andKynar®. In addition to these polymers, some types of special-applicationheat-shrink may also include an adhesive lining that may help to bondthe tubing to underlying electrodes and connectors, forming strong sealsthat may be waterproof or gas-tight sufficient to maintain the requiredpressure inside the ion transfer tube 20. In one embodiment, theheat-shrink tubing may have conductive polymer thick film to provideselectrical connections between the two or more electrodes without theneed to soldering, to shield the electromagnetic field produced by theRF voltages of the ion transfer device 20.

The sample, as shown in FIG. 2B, may be any arbitrary sample underanalysis or test, which the ion source probe 22 produces ions from, suchas a biological sample, a human or animal tissue, or any sample ofinterest that includes trace amounts of analyte of interest, or ageological sample. The sample may be a human body part for example ahuman hand, for example, being screen for skin cancer. The ion transferdevice 20 may have a plurality of bend positions 12 a, 12 b, 12 c.

FIG. 2C shows a block diagram of a conventional mass spectrometer 23such that the ion source is detached from the mass spectrometer and theions produced in an ionization probe 26 are transferred to the massspectrometer 23 via a flexible or re-configurable ion transfer device 20in accordance with embodiments of the present disclosure. A conventionalmass spectrometer 23 is used and the ionization source of the massspectrometer (which is directly attached to the mass spectrometer 23 inplace of an adapter 24) is replaced with an ion transfer device 20including the adapter 24 on one end (on the ion outlet side) that isconnected to the mass spectrometer 23 and an ionization probe 26 at theother end of the ion transfer device 20 (on the ion inlet side). In oneembodiment, the adapter 24, the ion transfer device 20, and theionization probe 26 replaces conventional ion source assemblies providedby mass spectrometer manufacturers (not shown—normally connected wherethe adapter 24 is connected in FIG. 2C) of the mass spectrometer 23.This configuration allows using an ionization probe 26 that can beextended to a distance, for example in a range from 0.1 to 10 mdepending on a length of the ion transfer device 20, from the massspectrometer 23, thus enabling easy scanning and analysis of differentareas of an object under test 27.

The ion transfer device 20 efficiently transfers the ions produced bythe ionization probe 26 to the mass spectrometer 23. The flexible orre-configurable ion transfer device 20 is connected to the massspectrometer 23 with the adapter 24 that is designed to fit theionization source inlet of the mass spectrometer 23 (where the adapter24 is connected in FIG. 2C). The ionization probe 26 may be an ambientionization source, atmospheric pressure ionization source, or a reducedpressure ionization source, which is hand-held, which may be easily heldwith a hand 25 of an operator and moved freely to different locations orparts of an object under test 27. For example, the ionization probe 26may be freely moved to different parts of a human body so that theionization probe 26 may become in contact with skin of different partssuch as hand or leg of a person 27 so that the ionization probe 26 mayproduce ions from human skin that is transferred to the massspectrometer 23 by the ion transfer device 20 for analysis by the massspectrometer 23.

The flexibility of the ion transfer device 20 enables using a hand-heldionization probe 26 and provides several advantages not available inconventional mass spectrometers, thus extending the use of such massspectrometry systems to many new applications. Because conventional massspectrometers are bulky and because ionization sources in conventionalmass spectrometers are directly attached to the mass spectrometer,therefore, in order to analyze human skin with conventional massspectrometers, the human must move and bring various body parts directlyin front of a conventional mass spectrometer. That can be difficult,impractical, or impossible. The flexible ion transfer device 20, asdisclosed herein, makes it possible for the ionization probe 26 toflexibly and freely move to different body part located away from themass spectrometer 23. This enables using conventional mass spectrometersin new applications, such as hospitals and medical offices, for example,for real-time skin analyses by replacing the conventional ion sourceswith the ionization probe 26 which is connected to the mass spectrometer23 via the flexible ion transfer device 20. Therefore, the massspectrometer 23 may be located far from the place where thesampling/ionization is taking place by the ion source probe 26. Forexample, the mass spectrometer 23 may be placed in a separate room andthe ion transfer device 20 may transfer the ions using the ion transferdevice 20 that is passed through a wall that separates the massspectrometer 23 from the object under test 27. Further, this approachenables efficient transfer of ions to the mass spectrometer 23 withoutor with minimal ion loss, resulting in increased analytical performance,such as increased detection limits and sensitivities required for manyapplications such as in situ human tissue analysis. In other words, theion transfer device 20 enables extending the ion source 26 of the massspectrometer 23 away from a mass spectrometer to enable sample analysisfrom objects 27 that are difficult to bring close to the massspectrometer 23. The object under test 27 may be a patient that is goingthrough surgery on a hospital bed. The ion transfer device 20 may have aplurality of bend positions 12 a, 12 b, 12 c, 12 d, 12 e around whichthe ion transfer device 20 may form a plurality of curvatures.

FIG. 2D shows a block diagram of a mass spectrometer 23 such that theion source is detached from the mass spectrometer and the ions producedin an ionization probe 26 are transferred to the mass spectrometer 23via a re-configurable ion transfer device 20 in accordance with one ormore embodiments of the present disclosure. The ionization probe 26 maybe held by a hand 25 of an operator or a user (or for example by arobotic arm of a robot) and a surface of interest 28 may be analyzedwithout having the mass spectrometer 23 close to the surface of interest28. The length of the ion transfer device 20 may be greater than 10 cm,50 cm, 100 cm, 150 cm, or 200 cm. In other embodiments, the length ofthe ion transfer device 20 may be greater than 2 meters, 5 meter, or 10meter, or more.

The ionization probe 26 produces ions from the surface of interest 28and the produced ions are transferred via the ion transfer device 20 tothe mass spectrometer 23 for analysis. As noted above, this enablesmodifying the conventional mass spectrometer 23 by replacing theoriginal ion source (not shown) of the conventional mass spectrometer 23by an adapter 24 that connects the ion transfer device 20 to the massspectrometer 23 and efficiently transfers the ions from the ion transferdevice 20 to the mass spectrometer 23. This allows use of ionizationprobes 26 that may be freely moved around to scan one or more surfacesof interest 28. For example, at an airport, this ionization probe may beused by a security office at a check point to scan for traces ofexplosive materials on passengers, cargo, or luggage. In a rover forplanetary exploration in space application, such a configuration enablesplacing the ion source 26 on a robotic arm and placing the massspectrometer 23 on a body of the rover. The ion source 26 may be used ina manufacturing line to monitor for the quality or contamination ofproduced products, such as pharmaceutical products in the productionline with one or more ionization sources 26 connected with one or moreion transfer devices 20 to one or more mass spectrometers 23. The iontransfer device 20 may have a plurality of bend positions 12 a, 12 b, 12c, 12 d around which the ion transfer device 20 may form curvatures.

FIG. 2E and FIG. 2F show two block diagrams of a mass spectrometrysystem such that the ion source 21 is detached from the ion guide 13 andthe ions are transferred to ion guide 13 via a re-configurable iontransfer device 20 in accordance with one or more embodiments of thepresent disclosure. The flexible ion transfer device 20 may have anadapter 14 (including one or more electrodes such as skimmer and samplecones disposed inside, or conventional ion funnels and ion guides) thatconnects to the ionization probe 21 and efficiently transfers ions fromthe ionization probe 21 to the flexible ion transfer device 20. Theadapter 14 may also include the electronics necessary to operate the iontransfer device 20, including direct current (DC), alternating current(AC), or radio frequency (RF) voltages for operation of the ion transferdevice 20. In one embodiment, the ion transfer device 20 may beconnected to a second adapter 16 that connects the ion transfer device20 to an ion guide 13 of a mass spectrometer. The second adapter 16 maybe used to attach the ion transfer device 20 to the mass spectrometer ina vacuum-tight manner while efficiently transferring the ions from theion transfer device 20 to the mass spectrometer. The second adapter 16may include electronics necessary to operate the ion transfer device 20(such as RF and DC voltage power supplies and the related control unitfor controlling the power supplies) or may include one or moreelectrodes floated at a voltage (such as skimmer and sample cones, orone or more conventional ion funnels) for efficient transfer andextraction of ions from the ion outlet of the ion transfer device 20 tothe ion guide 13 of the mass spectrometer. The first adapter 14 or thesecond adapter 16 may include electronics and other components necessaryto operate the ionization source 21, for example, connectors,electronics for plasma ionization, liquid reservoir for electrosprayionization or laser modules with fiber optics that may be attached tothe outer diameter or may be implemented along the ion transfer device20 for laser desorption/ionization, or a combination of them. Relatedwires and optical fibers may be attached to the ion transfer device 20to reach the ionization source 21 from the mass spectrometer or theadapter 16. This is advantageous for reducing the weight and size of theion source 21 that may be an ionization probe 26 used by an operator,which require reduced weight for easy handling by the operator.

FIG. 3A shows a block diagram of a mass spectrometry system such thatthe three ion sources 21 a-c are attached to a mass spectrometer via are-configurable ion transfer device 20 in accordance with one or moreembodiments of the present disclosure. Three ionization sources 21 a-c,which may be different or the same located at three different locations,are connected to an ion guide 13 of a mass spectrometer. The ionizationsources 21 a, 21 b, 21 c may be different or the same. One or moreionization sources 21 a, 21 b, 21 c may be connected to one or moresample preparation devices 29 to prepare the samples for ionization. Forexample, the ionization sources 21 a, 21 b, 21 c may be connected one ormore sample preparation or separation instruments, such as ahigh-pressure liquid chromatography system (LC or HPLC system) or a gaschromatography (GC) system to separate analytes before analysis with themass spectrometer. The ion sources 21 a, 21 b, 21 c are operated in amultiplexed manner and each ion source has a periodic allocated timeframe to introduce ions into the mass spectrometer via the correspondingion transfer tube that is attached to the ion source for analysis. Inthe present disclosure, the combination of the ion guide 13 the massanalyzer 15 and the detector 17 may be referred as the massspectrometer. This configuration provides the advantage that a singlemass spectrometer may be used to analyze different sample located indifferent places and coming from different separation or samplepreparation instruments as described above. Because analysis by a massspectrometer is performed in milliseconds to seconds, thus suchmultiplexing greatly enhances optimal use of mass spectrometers bycontinuously and sequentially providing ions from differentlocations/instruments or ionization sources 21 a, 21 b, 21 c to the massspectrometer for analysis.

FIG. 3B shows a block diagram of a mass spectrometry system such thatthe three ion sources 21 a-21 c are attached to two mass spectrometersvia re-configurable ion transfer devices 20 a-e in accordance with oneor more embodiments of the present disclosure. The ion processor 30(also referred to as the ion manipulation device in the presentdisclosure, an example of which is described in U.S. Pat. No. 9,966,244for lossless ion manipulation (SLIM)) may be used to selectivelytransfer the ions received from three ionization source 21 a, 21 b, 21 crespectively connected to three flexible ion transfer devices 20 a, 20b, 20 c to the ion processor 30. The ion processor 30 then selectivelytransfers the ions via two flexible ion transfer devices 20 d, 20 e totwo different mass spectrometers: the first mass spectrometer includingthe ion guide 13 a, the mass analyzer 15 a and the detector 17 a, andthe second one including the ion guide 13 b, the mass analyzer 15 b andthe detector 17 b, as shown in FIG. 3B. The ion processor 30 may trap,store, process (for example separate ions based on their mobility), andselectively transfers ion packets into these two mass spectrometers.

FIG. 4A shows a block diagram of an ion transfer device 20 in accordancewith one or more embodiments of the present disclosure. The ion transferdevice 20 may include an electrode unit 31 (each electrode unit maycompromise one or more independent conductive electrodes as disclosed inthe present application) connected to one or more voltages. The iontransfer device 20 may include an ion transfer enclosure 71. The iontransfer enclosure 71 may be a tube made from plastic or metal connectedto a voltage or ground in case the tube is made from metal or conductiveplastic. The enclosure 71 may be a plurality of tubes. The tube may becorrugated or in bellow form to allow flexible bending of the tube andthe ion transfer device 20 to produce a plurality of curvatures. Thetube may be constructed from one or more heat-shrink tubes. The iontransfer enclosure 71 (or simply referred to as the enclosure) maintainsthe one or more electrode units 31 in reduced pressure (or intermediatepressure below 760 Torr) and also provides a mechanical structure tosupport the electrode unit 31. The pressure level inside the enclosure71 may be maintained between in a range from 0.0001 Torr to 750 Torr,for example in a range from 0.1 to 10 Torr. A vacuum pump may beconnected to the enclosure 71 as with a T connector with an ion inlet(shown as ions in) and an ion source, with a T connector at an ionoutlet (shown as ions out) or one or more locations in between the ioninlet or the ion outlet along the enclosure 71, for example, in a middleportion of the enclosure 71. The pressure inside the ion transfer device20 may be the same or different at different locations inside theenclosure 71 along the ion transfer device 20. The pressure inside theenclosure may be in a range from 0.01 to 30 Torr. The electrode unit 31may be flexible for flexible bending along with the ion transferenclosure 71. The ion transfer device 20 may include one electrode unit31 having two or more electrodes, which may be flexible electrodes, suchas those shown, and described later in the present application, forexample, in FIG. 14A, FIG. 14B, FIG. 14C, FIG. 15A, FIG. 15B, FIG. 15C,and FIG. 16. In other embodiments, the one electrode unit includes aplurality of electrodes that are flexibly connected to each other or theenclosure 71, examples of which are shown in FIG. 6A, FIG. 6B, FIG. 6C,and FIG. 6D described later in the present application. The enclosure 71may be bent to have two or more different shapes or forms to have aplurality of curvatures (which may also be referred to as a plurality oftwists, arcs, or curves).

FIG. 4B and FIG. 4C show two block diagrams of embodiments of the iontransfer device 20 in accordance with one or more embodiments of thepresent disclosure. The ion transfer device 20 may include a pluralityof electrode units 31 a-c in FIG. 4B or 31 a-j in FIG. 4C that areconnected to each other. Each of the plurality of electrode units 31 a-jmay comprise a plurality of electrodes, which may be flexibleelectrodes, such as those shown, and described later in the presentapplication, for example, in FIG. 14A, FIG. 14B, FIG. 14C, FIG. 15A,FIG. 15B, FIG. 15C, and FIG. 16. In other embodiments, the ion transferdevice 20 may include a plurality of electrodes that are flexiblyconnected to each other or the enclosure 71, examples of which are shownin FIG. 6A, FIG. 6B, FIG. 6C, and FIG. 6D described later in the presentapplication. The plurality of electrode units 31 a-j and the enclosure71 may be flexible or bendable or reconfigurable from a first shape orconfiguration to a second shape or configuration. In one or moreembodiments, the plurality of electrode units 31 a-j may be not flexibleor re-configurable but flexibly connected to each other, such as thoseshown in FIG. 7A, FIG. 7B, FIG. 11B, FIG. 11C, FIG. 12A, FIG. 12B, andFIG. 13.

FIG. 4D shows a block diagram of an ion transfer device in accordancewith one aspect of the present disclosure. In one embodiment, aplurality of connecting electrodes segments 41 a-d, which areelectrically isolated from the plurality of electrode units 31 a-j, andmay be individually connected to different voltages, connect theplurality of electrode units 31 a-c. In one embodiment, the plurality ofconnecting electrodes segments 41 a-d may ensure efficient transfer ofions between two neighboring electrode units (31 a and 31 b) or (31 band 31 c). The plurality of connecting electrodes segments 41 a-d may bein form of skimmer cones or conductance limiting orifices and similarstructures used in differential pumping in conventional massspectrometers. In other embodiments, the plurality of connectingelectrodes segments 41 a-d, may be one or more conductance limitingorifices or a plurality of capillary tubes.

FIG. 5A, FIG. 5B, and FIG. 5C show three block diagrams of differentembodiments of the ion transfer device 20 connections to the massspectrometers 50,52,55 in accordance with one or more embodiments of thepresent disclosure. The ion transfer device 20 may include a pluralityof electrode units 31 a-j, as described above, that are connected toeach other. Each of the plurality of electrode units 31 a-j may beflexible or may be rigid and flexibly connected to each other, asdescribed above, and are located inside the enclosure 71. The pluralityof electrode units 31 a-j and the enclosure 71 may be bent to have twoor more different shapes or forms and may be reconfigurable or flexible.The ion transfer device 20 may be connected at one end to the ion sourceprobe 51 that may freely move in 3-dimensional space because of theflexibility of the ion transfer device 20. The ion source probe 51 maybe flexibly moved around to bring the ion source probe 51 close tosample or object under test to be analyzed. Further, the ion transferdevice 20 may be connected to ion guide and mass analyzer of a massspectrometer 50.

In one embodiment shown in FIG. 5B, an ion processor 54 may be includedand the ion processor (as describes above regarding U.S. Pat. No.9,966,244) may be connected to the ion source probe 53 on one end andthe mass spectrometer 52 on the other end using two different iontransfer devices 20 a and 20 b so that flow or pre-separation of ions(based on their ion mobility in the ion processor 54) may be controlled.FIG. 5C is similar to FIG. 5B with the difference that the ion processor59 is connected to two different ion sources 56 a,56 b, and multiplexesthe ions received from these two ion sources to the mass spectrometer55.

FIG. 6A, FIG. 6B, FIG. 6C, and FIG. 6D show perspective views of anembodiment of the flexible or re-configurable ion transfer device 20 inaccordance with one or more embodiments of the present disclosure. Inone or more embodiments, the plurality of electrodes 63 each having acentral hole 65 (of the same or different diameter, in one embodimentascending or descending diameters, which may also act as conductancelimiting orifice to limit gas flow between two adjacent electrode unitsand provide differential pressure in two adjacent electrode units) maybe connected to each other using flexible or elastic rods 61 a-d, whichgo through a plurality of holes 62 provided on each of the plurality ofthe electrodes 63. The plurality of electrodes 63 are disposed inside aflexible tube or enclosure 67. (The tube or enclosure 67 is not shown inFIG. 6C, FIG. 6D, FIG. 7A, and FIG. 7B for simplicity of illustration).This configuration allows the plurality of the electrodes to form one ormore curvatures around an axis 66 of the ion transfer device 20, asshown in FIG. 6C and FIG. 6D. The plurality of electrodes 63 each mayhave one or more electrical connection 68 to apply different voltages,such as RF voltages VRF1 and VRF2, and DC voltages, VDC1 and VDC2. Theplurality of electrodes 63 may be made from any metal (stainless steel,nickel, copper, gold, or any other metal with or without coatings) orany conductive material such as conductive plastic. The spacing betweenthe electrodes may be different or may be the same and may be a valuebetween 0.1 mm to 10 mm. The thickness of electrodes may be different ormay be the same and may be a value between 0.01 mm to 5 mm.

RF voltages may be applied by connecting a plurality of capacitors 70a,70 b in series to the electrical connections 68, which are connectedto electrodes 63, as shown in FIG. 6A and FIG. 6B. The capacitors 70a,70 b may have a value of 1 to 1000 pF. The DC voltages may be appliedby connecting resistors in series with the electrical connections 68, asshown in FIG. 6A. The resistor value may be 0.01M to 10M Ohms.

The capacitors and resistors may be connected by connectors, soldering,or spot-welding to the electrodes 63 or the electrical connections 68instead of using the electrical connections 68. Alternatively, thecapacitors 70 a,70 b and resistors 69 may be assembled on a separateflexible or rigid printed circuit board (PCB) and connected to theelectrodes, as shown in FIG. 8A, FIG. 8B, and FIG. 8C as described laterin the present application.

Application of DC voltage may be to the first and last electrodes of theplurality of electrodes 63, as shown in FIG. 6A by annotations VDC1 andVDC2. In one embodiment shown in FIG. 6B, each electrode of theplurality of electrodes 63 is connected to a separate controllable andaddressable DC voltage (VDC1 to VDC9) to provide different voltages toeach of the plurality of electrodes 63. The DC voltage may be any valuefrom 1 to 500 volts or greater than 500V. The RF voltages may be appliedas two out of phase RF voltages respectively connected to odd and evenelectrodes (VRF1 and VRF2). The amplitude of the RF voltage may be anyvalue from 1 to 500 volts or greater than 500V. The frequency of the RFvoltage may be any frequency from 50 KHz to 20 MHz. Preferably the RFand DC voltages should not cause gas breakdown at the pressure that theion transfer device 20 is operating at.

In one or more embodiments, the plurality of electrodes 63 are connectedto each other as shown in FIG. 6A but instead of using the flexible orelastic rods 61 a-d, a plurality of electrically insulating structures(for example elastic or rigid Viton or PTFE O-rings or any similarmaterial) are placed in between each two electrodes of the plurality ofelectrodes 63 (similar to the electrically insulating structures shownby annotations 92 a-d in FIG. 9A and FIG. 9B). Each of the electricallyinsulating structures, such as each O-ring, may be glued to one side ofeach electrode 63 to hold the electrically insulating structures inplace. This helps in prevent the electrically insulating structures frommoving or being exposed to the ions passing through the ion transferdevice 20, which may create charging problems if they end up ondielectric materials. In the flexible ion transfer device 20, theelectrically insulating structures are preferably not exposed to theions to avoid charging effects, which results from accumulation ofcharged particles on the electrically insulating structures, and mayreform the shape of electric fields, and therefore ion trajectories.Therefore, the inner diameters of the electrically insulating structuresare larger than the diameter of the holes 65, 72, 83 or 94) so that ifcharge accumulation occurs (for example on the electrically insulatingstructures shown by annotations 92 a-d in FIG. 9A and FIG. 9B), thecharge accumulation do not adversely affect the electric fields insidethe ion transfer device 20. In one embodiment, the resistors andcapacitors are directly connected to the electrodes 63 without theelectrical connections 68, similar to those shown in FIG. 8A, FIG. 8B,and FIG. 8C and the corresponding description later in this application.

To assemble the structure, the plurality of electrodes 63 and theelectrically insulating structures may be assembled on a cylindricalholder (not shown), and then upon assembly of the electrodes andconnecting the necessary electrical connections and components(resistors and capacitors), the assembly may be inserted into aheat-shrink tube (which is shown by annotation 67 in one or moreembodiments) so that by application of heat, the heat-shrink tube 67 toshrink and hold the assembly in place. Then, the cylindrical holder maybe removed. Such an assembly with heat-shrink tube holds the electrodesfirmly in place and also provides flexibility and re-configurability.Further, using heat-shrink tubing may eliminate the need for havingelectrically insulating structures (for example annotations 92 a-d inFIG. 9C) in between the electrodes to keep the electrodes separate asthe heat-shrink, upon application of heat and shrinking, holds theelectrodes in place and acts like electrically insulating structures tomake the electrodes in place while providing the flexibility asdisclosed in the present application, as shown in FIG. 9C, in which theheat-shrink tube shrink into the area in between two adjacent electrodes91.

FIG. 7A and FIG. 7B show perspective views of the flexible orre-configurable ion transfer device 20 in accordance with one or moreembodiments of the present disclosure. In this exemplary embodiment,instead of having all of the plurality of electrodes flexibly attachedto each other (like those embodiments shown in FIG. 6A, FIG. 6B, FIG.6C, and FIG. 6D), the ion transfer device 20 may include electrodeassemblies (or units) 77 a, 77 b, 77 c in which the electrodes 74 arerigidly attached to each other, and the electrode units 77 a, 77 b, 77 c(electrode units are also referred to as electrode assemblies in thepresent disclosure) are flexibly attached to each other. The pluralityof electrodes 74 each having a central hole 72 may be connected toadjacent electrodes using rigid rods 61 a-d, which go through aplurality of holes 72 provided on each of the plurality of theelectrodes 74. In other embodiments, the electrodes 74 may be fixed toeach other with glue, epoxy, or screws while maintaining a predeterminedspacing in a range of 0.05 to 5 mm between the electrodes 74. Theelectrode assemblies (units) 77 a, 77 b, 77 c are flexibly attached toeach other and provide the flexibility.

FIG. 8A, FIG. 8B, and FIG. 8C show front views of three embodiments ofthe electrodes of the flexible or re-configurable ion transfer device 20in accordance with one or more embodiments of the present disclosure. Inone embodiment shown in FIG. 8A, a printed circuit board (PCB) electrode82 of the plurality of electrodes may be made with PCB. The PCBelectrode 82 may include a plurality of holes 81 a-d that provide a pathfor the rods 61 a-d. A center hole 83 in the PCB electrode 82 provides apath for ions in the center area of the PCB electrode 82. Around thecenter hole 83, a metal track 84 acts as a conductive electrode forapplication of voltages to produce electric fields in and around thecenter hole 83 necessary for transferring ions. The metal track 84,which may be copper, or gold-immersion electrodes used in PCBmanufacturing similar to through-hole assemblies well-known in PCBproduction but with much larger diameter. The diameter of the hole 83may be a value between 0.2 inches to 10 inches. A resistor 86 a and acapacitor 86 b may be assembled on the PCB electrode 82 to provide thenecessary DC voltage and RF voltage, respectively. A plurality ofconnectors 85 a-b connect to adjacent PCB electrode 82 or DC and RFpower supplies to provide the required voltages.

In one embodiment shown in FIG. 8b , a PCB electrode 82 of the pluralityof electrodes 63 may be circular shape. One of ordinary skill in the artwould recognize that the electrodes may be made in any arbitrary shape.In one embodiment shown in FIG. 8C, a PCB electrode 82 of the pluralityof electrodes 63, instead of a plurality of holes 81 a-d that provide apath for the rods 61 a-d (as shown in FIG. 8A with annotations 81 a-d),the PCB electrode 82 may include a plurality of electrically insulatedstructures 88 a-d to flexibly connect two adjacent PCB electrodes 82.The plurality of electrically insulated structures 88 a-d may be madewith pogo-pins, or elastic balls, or O-rings attached to the board.

FIG. 9A, FIG. 9B, FIG. 9C, FIG. 9D, and FIG. 9E show cross section viewsof electrodes 91 of the flexible or re-configurable ion transfer device20 connected to each other in accordance with one or more embodiments ofthe present disclosure. The electrodes 91 may be stacked on each other,as shown in FIG. 9A and may be centered around an axis 96, which maycross the centers of holes 94 on electrodes 91. A plurality of spacers92 a-d may be placed in between the electrodes 91 to provide therequired spacing between electrodes and also the re-configurability andflexibility. The electrodes 91 may include a resistor 95 and capacitor93. This configuration provides flexibility for the ion transfer device20. The electrodes 91 each having an electrode axis 96 a-c may beflexibly bend around the axis 96. The degree of bending is defined asthe angle between the axis 96 and each electrode axis 96 a-ccorresponding to the plurality of electrodes 91. The degree of bendingmay be any value between 0.0001 to 5 degrees for each electrode 91. Insome embodiments, only some of the electrodes 91 may bend around theaxis 96. In some embodiments, instead of employing the plurality ofspacers 92 a-d, a heat-shrink tube 99 may keep the electrodes 91 inplace (electrically separated from each other) while maintainingflexibility. In other embodiments, both the plurality of spacers 92 a-d,and heat-shrink tube 99 may keep the electrodes 91 in place whileproviding flexibility. The heat-shrink tube may also serve as theenclosure 71 to maintain the electrodes 91 in reduced pressure asdisclosed earlier in the present application. Although FIG. 9C showsonly one layer of heat-shrink tube 99, but one or more layers ofheat-shrink tube 99 may be provided to adjust flexibility and thepressure inside the ion transfer device 20. In one embodiment, aplurality of wires, which may be disposed outside or inside theenclosure 71 (which may be for example the heat-shrink tube 99) providerequired electrical radio frequency (RF), or direct current (DC)voltages (or constant voltage). The voltages may be provided in pulsedmode, with pulse durations of, for example, 0.1, 0.5, 1, 5, 10, 100, or1000 milliseconds. The pulsed voltages may be periodic, having a periodof 0.01, 0.1, 0.5, 1, or 2 seconds, or more than 2 seconds. In otherembodiments, a plurality of heat-shrink tubes may be provided, and theelectrical wires may be disposed in between the layers of theheat-shrink tube.

In one or more embodiment shown in FIG. 9D and FIG. 9E, instead of usingthe plurality of spacers 92 a-d (as shown for example in FIG. 9A), theelectrodes 91 may have matching extrusions 97, 98 on two sides of theelectrode 91 that are engaged with corresponding matching extrusions 97,98 of adjacent electrodes 91, as shown in FIG. 9D and FIG. 9E, toprovide flexibility as disclosed in the present application. One ofordinary skill in the art would recognize that this structure may bemanufactured by separate electrodes 91 flexibly connected to each otherand having many degrees of freedom such as those found in “snake robots”having many degrees of freedom or may be manufactured by rolling astructure having matching extrusions 97, 98 similar to those used inconventional flexible electrical conduits.

FIG. 10A and FIG. 10B show perspective views of individual electrodes ofthe flexible or re-configurable ion transfer device 20 in accordancewith one or more embodiments of the present disclosure. For simplicityof illustration, the enclosure is not shown in these figures. FIG. 10Aand FIG. 10B show a multipole ion guide that includes a plurality ofrods 103 connected to DC and/or RF voltages. Multiple ion guides mayhave any even number of rods, such as four, six, eight, etc that arehold in place with a plurality of rod holders 102, 104. Two conductancelimiting plates 101, 105 having an orifice 107 are attached at the twoends to the rod holders 102, 104. The conductance limiting plates 101,105 may be connected to DC or RF voltages (for example at a frequency of0.1 MHz to 10 MHz). A plurality of electrically insulating pieces 106(which may be made by elastic materials such as Viton) may be connectedto the conductance limiting orifices 105 to provide flexibility. The oddand even numbers of the plurality of rods 103 are respectively connectedto two out of phase RF voltages. A DC offset voltage may be applied toall of the rods 103.

FIG. 11A, FIG. 11B, and FIG. 11C show perspective views of threeelectrodes of the flexible or re-configurable ion transfer device 20connected to each other in accordance with one or more embodiments ofthe present disclosure. In one embodiment, the ion transfer device 20may be constructed with multipole ion guides (each acting as oneelectrode unit) flexibly attached to each other. A plurality ofindividual electrodes (each electrode including the components as shownin FIG. 10A and FIG. 10B) may be connected to each other as shown inFIG. 11A, FIG. 11B, and FIG. 11C to provide a flexible ion transferdevice 20. The two conductance limiting plates 105 on two adjacentelectrodes are connected to each other with the plurality ofelectrically insulating pieces 106 placed in between to provideflexibility. In another embodiment, the two electrodes or multipole ionguide structures may be connected to each other with the structure shownin FIG. 9A and FIG. 9B to provide flexibility. Heat-shrink tubes mayalso be used as enclosure and are not shown for simplicity ofillustration.

FIG. 12A and FIG. 12B show perspective views of seven electrodes of theflexible or re-configurable ion transfer device 20 connected to eachother in accordance with one or more embodiments of the presentdisclosure. In one embodiment, the electrodes may have a plurality ofcurvatures or bends around an axis 110 of the ion transfer device 20.The enclosure is not shown in this figure for simplicity ofillustration. The flexibility of this structure may be similar to thoseshown in FIG. 7A and FIG. 7B.

FIG. 13 shows a perspective view of two electrodes of the flexible orre-configurable ion transfer device 20 connected to each other inaccordance with one or more embodiments of the present disclosure. Inone embodiment, the multipole ion guides may include a plurality of rods130 that are hold in place with a rod holder 131. To provideflexibility, the rods 130 of the two adjacent electrodes are connectedflexibly to each other as shown in FIG. 13 with a plurality ofconnecting pieces 132. The plurality of conducting pieces connect twocorresponding rods 130 to each other. The plurality of connecting pieces132 may be conductive or electrically insulating, which may be made by,for example, connecting the rods with flexible epoxy. In anotherembodiment, the plurality of rods 130 may be flexible while maintaininga constant or semi-constant distance between two adjacent rods in anelectrode assembly to provide a flexible ion transfer device 20.

FIG. 14A, FIG. 14B, and FIG. 14C show perspective views of an enclosure141 and two different electrode geometries of the flexible orre-configurable ion transfer device 20 in accordance with one or moreembodiments of the present disclosure. FIG. 15A, FIG. 15B, and FIG. 15Cshow perspective views of three embodiments of the flexible orre-configurable ion transfer device 20 in accordance with one or moreembodiments of the present disclosure. In one embodiment, the enclosure21 may be made of a flexible tube 141 having an inner surface 142 asshown in FIG. 14A. A plurality of ring electrodes 145, as shown in FIG.14B, are connected to a plurality of DC and RF voltages (not shown forsimplicity of illustration) may be disposed inside the flexible tube 141to provide the ion transfer device 20. Each of the plurality of ringelectrodes 145 may include an inner surface 143 and an outer surface144. The outer surface 144 may be disposed on the inner surface 142 ofthe flexible tube 141 to provide an ion transfer device 20 as shown inFIG. 15A. In another embodiment, a plurality of elongated electrodes 148(any even number of electrodes) having an outer surface 147 and an innersurface 146 may be disposed in the flexible tube 141. FIG. 15B shows anexample of the ion transfer device 20 according to this exemplaryembodiment. The ring electrodes 145 and the elongated electrodes 148 areflexible and may bend when the flexible 141 tube bends. The flexibletube 141 may be made with a heat-shrink tube that has a sticky innersurface 142 for sticking to the outer surface 144 of the ring electrodes145 or the outer surface 147 of the plurality of elongated electrodes148 to the inner surface 142 of the flexible tube 145. FIG. 15C show across section of another embodiment of a flexible ion transfer device 20which may be made with bellow tube 151 and a plurality of electrodes 152may be place inside the bellow tube 151. In this embodiment, a pluralityof ground electrodes 151 prevent ions from charged build-up on thebellow tube 151. Although these embodiments are shown in straight form,one of ordinary skill in the art, in view of the present disclosure,would understand and appreciate that these structures provideflexibility and may be bent to any form or shape similar to aconventional hose.

FIG. 16 shows a perspective view of electrode geometry in an embodimentof the flexible or re-configurable ion transfer device 20 in accordancewith one or more embodiments of the present disclosure. The flexible iontransfer tube 20 may be constructed with two wires 161, 162 (or aplurality of the two wires 161, 162) that are wound around an axis 163into helix structures having a diameter with any value in the range of0.2 to 6 inches. The two wires are connected to RF voltages at afrequency of 0.05 to 10 MHz and amplitudes of, for example, 50V. Theamplitude may be any value between 1 to 1000V. The enclosure is notshown in FIG. 16 for simplicity of illustration but similar flexibletubes, or heat-shrink tubes disclosed earlier in the present applicationmay be used. The ion transfer device 20 made with the electrodes shownin FIG. 16 is flexible and may have several curvatures along the lengthof the ion transfer device 20. As noted above, the pressure of the iontransfer tube may be in the range of, for example, 0.001 to 760 Torr.

FIG. 17A and FIG. 17B show two side views of ion trajectory simulationin an embodiment of the flexible or re-configurable ion transfer device20 in accordance with one or more embodiments of the present disclosure.Ion trajectory simulations were performed with SIMON® software and theresults are shown in FIG. 17A (side view) and FIG. 17B (top view). Thesimulations were performed in a pressure of 1 Torr and the simulationresults demonstrated that the electrodes effectively trap the ions,producing an ion cloud 164, for a long period of time. The simulationswere performed in a bent structure of FIG. 16 around an axis 163. Avariety of RF voltages were applied at different frequencies andvoltages and the structure was functional in a wide range of parameters(voltage and amplitude of the RF voltage) and pressures (0.01 to 30Torr).

FIG. 18 shows RF and DC voltage waveforms applied to the electrodes ofthe flexible or re-configurable ion transfer device in accordance withone or more embodiments of the present disclosure. In the fivesequential graphs shown in FIG. 18, the times are shown by t1 to t5, t1graph being the first wave form of the sequence and t5 being the lastwave form of the sequence. The time period between each graph may be thesame or different. For example, the time difference between t1 and t2may be in the order of milliseconds (ms) or seconds (s), and may be anyvalue between 0.1 ms to 10 s.

The electrode units 31 a-d may comprise any electrode configuration,geometry, shape, or form disclosed in the present application. Theplurality of electrode units 31 a-d may be those disclosed in FIG. 6A,in which every even and odd electrode is connected to two out of phaseRF voltages respectively. Two out of phase RF voltages are applied totwo adjacent electrodes. For example, in a multipole ion guide, one ofthe two out of phase RF voltages is applied to every other electrode andthe other of the two out of phase RF voltages is applied to theremaining electrodes. RF voltages of the ion transfer device 20 pushesthe ions radially toward the centerline or an axis of the ion transferdevice 20 as disclosed and shown above in exemplary embodiments, and asfor example shown in the simulation results of FIG. 17A and FIG. 17B,which is an RF only simulation. The radial force is provided via aneffective potential from RF voltages or waveforms on the electrodes. TheRF waveforms effectively keep ions off the plates. The DC voltages pushions axially toward the two ends of the ion transfer device 20. Theapplied RF voltages trap ions around an axis and inside the ion transferdevice 20.

In FIG. 18, DC voltages are illustrated with solid lines and the RFvoltages are illustrated with a sine or zigzag waveform. Although the DCand RF voltages are illustrated separately for simplicity ofillustration, one of ordinary skill in the art would understand thatthese two wave forms may be combined, superimposed or added byapplication of the RF voltages via a capacitor to the DC voltages. TheDC voltage sources providing the DC voltages may require RF chokes toprevent the RF voltage from penetrating into the DC power supply. The DCvoltages may also be regarded as the DC offset voltage applied to the RFvoltage. The RF voltage (two out of phase sin waveform applied forradially pushing the ions towards a center of the ion transfer device20) may always be present in the electrodes of the ion transfer device20. Alternatively, the RF voltage may only be present when ions existsin the related electrodes of the ion transfer device 20.

The term “electrode unit” in the present application is defined as anumber of electrodes that contain an ion packet, for example ion 1 orion 2 as shown in FIG. 18. Each of the electrode units 31 a-d is anelectrode unit that may contain any number of electrodes but trap andcontain an ion packet as described earlier in the present application.

In t1, two packet of ions, ions 1 and ions 2, are held in DC potentialwells created in electrode units 31 a and 31 c at V1 voltage. The ions 1and ions 2 may be from the same ion source or from different ionsources. Also, the ions 1 and ions 2 may contain the same or differenttypes of ions obtained from the same or different samples by theionization source. The DC voltage at electrode unit 31 b and 31 d are atV3, which is greater than V1. Therefore, the DC voltages of theelectrode units 31 b and 31 d act as a potential barrier and prevent thetwo ions packets (which may be in the form of ion clouds or ionpopulation) from mixing with each other. The values of DC voltages maybe any positive value in a range from 0.1V to 1000V.

In t2, the DC voltage of the electrode unit 31 d is reduced from V3 toV1, thus allowing the ions 2 to axially expand to the adjacent electrodeunit 31 d (the ions are still radially contained with the RF voltages—infact, the ions 1 and ions 2 are always contained in the centerline by RFvoltages as described above). The potential well of the electrode 31 bprevents the ions 1 and ions 2 from mixing with each other.

In t3, the DC voltage on electrode unit 31 c is increased from V1 to V3thus forcing or pushing the ions 2 into the electrode unit 31 d.Therefore, the ions 2 are shifted one electrode unit to the right.

In t4, the DC voltage of the electrode unit 31 b is reduced from V3 toV1, thus allowing the ions 1 to axially expand to 31 b electrodes. Thepotential well of the electrode 31 c prevents the ions 1 and ions 2 frommixing with each other.

In t5, the DC voltage on electrode unit 31 a is increased from V1 to V3thus pushing the ions 1 into the electrode 31 b. Therefore, the ions 1are also shifted one electrode unit to the right (where the ion outletof the ion transfer device 20 is located in this exemplary embodiment).

During the sequences from t1 to t5, two separate ion packets, ions 1 andions 2 are shifted one electrode unit from the ion inlet side of the iontransfer device (on the left) to the ion outlet side of the ion transferdevice 20 (on the right). Therefore, this sequence enables sequentiallypacking and efficiently transferring the ions or ion clouds via theflexible ion transfer device 20 without these ion packets being mixed.The ion transfer may be performed in a sequential manner and the ions,in the form of ion packets, may be transferred from the inlet to theoutlet of the ion transfer device 20 sequentially. Further, thissequence also allows arrangement of ions produced from different ionsources or produced from the same ion source but from different samples,into ion packets. Although in each time frame of t1 to t5 of FIG. 18 theDC voltage values V1 and V3 are used each electrode 31 a-d may have adifferent voltage value and they do not need to be necessarily the same.

FIG. 19 shows RF and DC voltage waveforms applied to the electrode unit31 of the flexible or re-configurable ion transfer device 20 inaccordance with one or more embodiments of the present disclosure. TheRF and DC voltages are described in detail with respect to FIG. 18, andthe same description is applicable to FIG. 19. The electrode 31 maycomprise of a plurality of ring electrodes similar to those shown inFIG. 6A, FIG. 6B, and FIG. 6C. In exemplary embodiment shown in FIG. 19,DC voltages are individually controlled and applied to each electrode ofthe electrode unit 31. In the following, the applications and shiftingof ion packets are described for the electrode unit 31 with ringelectrodes similar to those shown in FIG. 6A but one of ordinary skillin the art would understand and appreciate that the shifting of ionpackets may also be realized with other electrode geometries of the iontransfer device 20 as disclosed in the present application.

In this exemplary embodiment, each electrode unit is one electrode, forexample one ring electrode (shown in FIG. 6A) is one electrode unit, andthe shifting of the ion packets are performed in one electrode unit ateach time period (t1 to t5).

In t1, four packet of ions, ions 1, ions 2, ions 3, and ions 4 (in theform of ion packets), are trapped separately by DC potential wellscreated in electrode unit 31 created by application of V3 to four of thering electrodes which are spatially separate (first group of ringelectrodes of the electrode unit 31). In FIG. 19 and at t1, first groupof ring electrodes are held at DC voltage V3 and the remainingelectrodes are at held at V1.

In t2, the ring electrodes adjacent and to the right of the first groupof ring electrodes (second group of electrodes) are switched to V3 fromV1, and shortly after, the first group of electrodes are switched to V1.

In t3, the ring electrodes adjacent and to the right of the second groupof ring electrodes (third group of electrodes) are switched to V3 fromV1, and shortly after, the second group of electrodes are switched toV1.

In t4, the ring electrodes adjacent and to the right of the third groupof ring electrodes (fourth group of electrodes) are switched to V3 fromV1, and shortly after (for example tens of micro seconds to millisecondsor seconds), the second group of electrodes are switched to V1.

As a result, the ion packets move sequentially in the ion transferdevice 20 from left (the ion inlet) to the right (the ion outlet) whilekeeping the ion packets separate, for example by a traveling DC voltagepulse while the RF voltages maintain the ions around an axis of the iontransfer device 20.

The wave form of FIG. 19 is similar to the wave form of FIG. 18 with thedifference that each electrode is individually connected to addressableDC voltages in FIG. 19. In FIG. 18, a group of electrodes are connectedto the same DC voltage. Therefore, sequential transfer of ions accordingto FIG. 18 may require smaller number of individually addressable DCvoltages compared to that described in FIG. 19, as in the embodiment ofFIG. 19, all individual electrodes must be individually connected tocontrollable DC voltages.

FIG. 20 shows a flow chart of a method of transferring ions with theflexible or re-configurable ion transfer device in accordance with oneor more aspects of the present disclosure. In one embodiment, a methodfor transferring ions includes producing ions from a sample in step S1,transferring the ions with at least one ion transfer device that isconfigured to be flexible or re-configurable in step S2, the iontransfer device having an enclosure, and a plurality of electrodesdisposed at least in part inside the enclosure; separating the ions withat least one analyzer configured to separate the ions based on mobilityor mass to charge ratio in step S3; and detecting the separated ionswith at least one detector in step S4. The transferring of the ions maybe realized by the method and application of the waveforms describedwith relation to FIG. 18 and FIG. 19 to the ion transfer device 20.

FIG. 21 shows a block diagram of control unit 210 for ion transferdevice 20 in more detail upon which an embodiment of the presentdisclosure may be implemented. The ion transfer device 20 may include ormay be connected to one or more control units 210. The control unit 210includes a memory 211, a processor 212, an input/output (I/O) interface213 that is connected to a display 214 and a keyboard 215, an interface217 that is connected to RF voltage generator 218 and DC voltagegenerator 219. The control unit 210 includes one or more memory 211,such as a random-access memory (RAM) or other dynamic storage device(e.g., dynamic RAM (DRAM), static RAM (SRAM), and synchronous DRAM(SDRAM)), coupled to the bus 216 for storing information andinstructions to be executed by processor 212. In addition, the one ormore memory 211 may be used for storing temporary variables or otherintermediate information during the execution of instructions by theprocessor 212. The control unit 210 may further include a read onlymemory (ROM) or other static storage device (e.g., programmable ROM(PROM), erasable PROM (EPROM), and electrically erasable PROM (EEPROM))coupled to the bus 216 for storing static information and instructionsfor the processor 212. The control unit 210 may further include acommunication interface 221 coupled to the bus 216. The communicationinterface 221 provides a two-way data communication. For example, thecommunication interface 221 may be a network interface card to attach toany packet switched LAN. As another example, the communication interface221 may be an asymmetrical digital subscriber line (ADSL) card, anintegrated service digital network (ISDN) card, a Universal Serial Bus(USB), or a modem to provide a data communication connection to acorresponding type of communications line. A wired or wireless networkmay further be connected to the communication interface 221 connected toone or more computers that provide one or more operators and/or users aplatform to communicate with the control unit 210. The control unit alsoincludes an interface 217 that translates digital data received from thebus 216 and transmits instructions to one or more RF voltage generators218 and one or more DC voltage generators 219, which provide the RF andDC voltages for operation of the ion transfer device 20. The RF voltagegenerators 218 and DC voltage generators 219 receive the instructionsfrom the interface 217 and produce the voltages required by the iontransfer device 20. In one embodiment, the interface 217 may also beconnected to a mass spectrometer that is connected to the ion transferdevice 20 to, for example, synchronize to adjust the timing andmultiplexing of the ion transfer process according to those described inrelation to FIG. 18 and FIG. 19. The interface 217 may also be connectedto one or more ionization probes to synchronize production and transferof ions from a sample.

While the present disclosure has been described above with respect to alimited number of embodiments, those skilled in the art, having thebenefit of this disclosure, will appreciate that other embodiments maybe devised which do not depart from the scope of the invention asdisclosed herein. Accordingly, the scope of the invention should belimited only by the attached claims.

What claimed is:
 1. An ion analysis system comprising: one or moreionization sources that produce ions; one or more analyzers that analyzethe ions based on ion mobility or mass to charge ratio of the ions; andone or more ion transfer devices connected between the one or moreionization sources and the one or more analyzers, the one or more iontransfer devices having a plurality of electrodes configured to beflexible or flexibly connected to each other, and the one or more iontransfer devices being configured to be flexible or re-configurablewhile transferring the ions.
 2. The ion analysis system according toclaim 1, wherein two or more of the ionization sources produce the ionsby two or more different ionization mechanisms.
 3. The ion analysissystem according to claim 1, wherein the ions produced by one of theionization sources are transferred to at least two of the analyzers foranalysis.
 4. The ion analysis system according to claim 1, wherein atleast two or more of the analyzers analyze the ions by at least two ormore different mechanisms.
 5. The ion analysis system according to claim1, wherein two or more of the ionization sources produce the ions fromsamples located at different locations.
 6. The ion analysis systemaccording to claim 1, wherein one of the analyzers receives the ionsfrom two or more of the ionization sources in a multiplexed manner. 7.The ion analysis system according to claim 1, wherein each of theionization sources has a periodic allocated time frame to introduce ionsinto the one or more analyzers.
 8. The ion analysis system according toclaim 1, wherein the one or more ionization sources are connected to oneor more sample preparation or sample separation devices.
 9. The ionanalysis system according to claim 1, wherein the one or more iontransfer devices are connected to an ion processor, and the ionprocessor is connected to the one or more analyzers.
 10. The ionanalysis system according to claim 9, wherein the ion processorseparates the ions based on ion mobility prior to transferring the ionsto the one or more analyzers.
 11. The ion analysis system according toclaim 1, wherein the one or more ion transfer devices separate ionsbased on ion mobility while transferring the ions.
 12. A method for ionanalysis comprising: producing ions with one or more ionization sources;analyzing the ions with one or more analyzers based on ion mobility ormass to charge ratio of the ions; and transferring the ions from the oneor more ionization sources to the one or more analyzers by one or moreion transfer devices, the one or more ion transfer devices having aplurality of electrodes configured to be flexible or flexibly connectedto each other, and the one or more ion transfer devices being configuredto be flexible or re-configurable while the transferring.
 13. The methodaccording to claim 12, wherein the producing further includes producingthe ions by two or more different ionization mechanisms.
 14. The methodaccording to claim 12, wherein the transferring further includestransferring the ions produced by one of the ionization sources to atleast two of the analyzers for analysis.
 15. The method according toclaim 12, wherein the analyzing further includes analyzing the ions byat least two or more different mechanisms.
 16. The method according toclaim 12, wherein the producing further includes producing the ions fromsamples located at different locations.
 17. The method according toclaim 12, wherein the transferring further includes transferring theions to an ion processor and then transferring them to the analyzer. 18.The method according to claim 17 further comprising: separating the ionsin the ion processor based on ion mobility prior to transferring theions into the one or more analyzers.
 19. The method according to claim12, wherein the one or more ion transfer devices separate ions based onion mobility while the transferring.
 20. An ion analysis systemcomprising: one or more ionization sources that produce ions; one ormore ion transfer devices that transfer the ions, each ion transferdevice including a plurality of ring-shaped electrodes constructed fromprinted circuit board, each electrode being connected to an adjacentelectrode with spring connectors, each of the ring-shaped electrodeshaving at least one resistor and one capacitor; and the plurality ofelectrodes being enclosed inside one or more layers of tubing; and oneor more analyzers that analyze the ions based on ion mobility or mass tocharge ratio of the ions.